Disease relevance of SNORA62

• E2 binding sites are the major cis components of HPV-11 DNA replication, and there is evidence for synergy between these sites [1].
• Replication of all these plasmids was absolutely dependent on the presence of the HPV-18 E1 and E2 proteins [2].
• HPV-16 E2 expressed from intact episomes may act in trans to regulate integrated genome expression of E6 and E7 [3].
• The frequencies of genetic apo E isoforms E2, E3 and E4 were determined in 523 patients with myocardial infarction and compared to those in a control group (1031 blood donors) [4].
• Soluble extracts from uninfected murine cells supplemented with purified viral E1 and E2 proteins support the replication of exogenously added papilloma virus DNA [5].

Psychiatry related information on SNORA62

• E1/E2 dimers and the HCV-LPs of 1b did not bind CD81-LEL, consistent with the notion that CD81 recognition by E2 is strain-specific and does not correlate with permissiveness of infection [6].

High impact information on SNORA62

• The E2 transactivator stimulates the binding of the E1 replication protein to the minimal origin of replication and activates DNA replication [5].
• This complex bound specifically to the viral origin of replication, which contains multiple binding sites for E2 [7].
• The E2 protein serves these functions by tethering papillomavirus episomes to mitotic chromosomes; however, the mechanism remains unresolved [8].
• Viral genomes encoding this E2 mutation are not episomally maintained in cell culture [8].
• RNAi-induced depletion of ChlR1 significantly reduced E2 localization to mitotic chromosomes [8].

Chemical compound and disease context of SNORA62

• Antibodies to E1 and E2/Protein X components of pyruvate dehydrogenase complex in sera of patients with primary biliary cirrhosis [9].
• CONCLUSION: Continuous-combined formulations of E2 1 mg with norethindrone acetate 0.1, 0.25, or 0.5 mg are associated with a low incidence of uterine bleeding [10].
• Using this system, a recombinant virus expressing the E2 glycoprotein of classical swine fever virus (CSFV) was produced [11].
• CONCLUSION: The results of this study support the safety and efficacy of this unique HRT regimen and suggest that the minimal NGM dose required to protect the endometrium from hyperplasia in a pulsed progestin regimen consisting of continuous E2 1 mg is 90 microg [12].

Biological context of SNORA62

• Binding of E1 to the origin was increased by E2 proteins and required the presence of E2 binding sites [13].
• To examine the interplay of these replication proteins, we have analyzed the binding of human papillomavirus (HPV) type 31b E1 and E2 proteins to the origin of replication [13].
• These observations suggest a model whereby modulation of the relative levels of E1 and E2 during the viral life cycle may alter the pattern of origin binding and possibly episomal copy number [13].
• The origins of DNA replication in bovine and human papillomavirus genomes have been localized to a specific part of the upstream regulatory region (URR) which includes recognition sites for E1 and E2 proteins [1].
• Sequence components adjacent to the E1 and E2 binding sites, comprising AT-rich and purine-rich elements and the consensus TATA box sequence, probably contribute to the overall efficiency of replication, though they are nonessential [1].

Anatomical context of SNORA62

• To address the mechanisms by which the viral DNA is stably propagated in the transformed cells, we have constructed a cell line CH04.15 expressing constitutively the viral proteins E1 and E2, that are required for initiation of viral DNA replication [14].
• In this study, we have corrected this mutation and have evaluated the effect of mutations of either the E1 or the E2 gene on the efficiency of HPV-16 immortalization of human keratinocytes [15].
• The human E1 alpha and the previously isolated human E2 cDNAs were used as probes in Northern blot analysis with cultured fibroblasts and lymphoblasts from seven unrelated MSUD patients [16].
• This association may explain the ability of E2 protein to activate transcription, since GRP78 has been postulated to be a sensor of stress in the endoplasmic reticulum [17].
• Since overexpression of GRP78 has been shown to decrease the sensitivity of cells to killing by cytotoxic T lymphocytes and to increase tumorigenicity and resistance to antitumor drugs, this activity of E2 protein may be involved in the pathogenesis of hepatitis C virus-induced diseases [17].

Associations of SNORA62 with chemical compounds

• Several amino acid substitutions in the phosphate-binding loop (P loop), which is implicated in binding the triphosphate moiety of ATP, abolished E2 binding, indicating that the structural integrity of this domain is essential for the interaction [18].
• No evidence of O-linked glycans was found on either the E1 or the E2 glycoprotein [19].
• The monovalent ionophore monensin, which inhibits intracellular transport of proteins through the ER-Golgi complex, was used to block the transport of E1 and E2 glycoproteins through the Golgi complex [20].
• For O-linked glycosylation, addition of N-acetylgalactosamine and galactose to E2 protein was found to take place in the medial to the trans Golgi [20].
• Significant loss of antigenicity (greater than 90%) of RV E1 and E2 proteins was observed when IB assays were performed in the presence of 2-mercaptoethanol as compared with assays under nonreducing conditions [21].

Physical interactions of SNORA62

• The mechanism by which these proteins are recruited to the origin and the role of the E1/E2 complex in replication remain undefined [13].

Regulatory relationships of SNORA62

• Binding of the human papillomavirus E1 origin-recognition protein is regulated through complex formation with the E2 enhancer-binding protein [13].
• The results suggest that immunization of Ad.CMV.HCV virus combined with E2 protein is an effective modality to induce humoral as well as cellular immune response to E2 antigen [22].
• These results suggest that YY1 can inhibit HPV ori replication by interfering with E2 protein functions [23].
• The E2 protein expressed in both insect and mammalian cells was a glycoprotein of 60 kDa (gp60) and removal of the sugar residues by N-glycanase yielded 38- and 40-kDa proteins [24].

Other interactions of SNORA62

• Therefore, changes in the relative amounts of E1 and E2 proteins can dramatically alter the pattern of binding of viral replication factors to the origin [13].
• Abrogation of a mitotic checkpoint by E2 proteins from oncogenic human papillomaviruses correlates with increased turnover of the p53 tumor suppressor protein [25].
• The sera of mice immunized with the E1E2 inhibited the binding of E2 protein to the major extracellular loop of human CD81 [22].

Analytical, diagnostic and therapeutic context of SNORA62

• Isothermal titration calorimetry and changes in protein fluorescence showed that the inhibitors bind to the transactivation domain of E2, the region that interacts with E1 [26].
• Levels and functional affinities of IgG specific for individual RV proteins (E1, E2, and C) were measured by enzyme immunoassay (EIA) [27].
• The viral copy number/cell was assessed by dot-blot hybridization and the presence of E1/E2 genes by PCR and Southern blot [28].
• Immunofluorescence microscopy combined with immunoprecipitation and endoglycosidase treatment of cells infected with the HSV-1-based vectors expressing E1 and E2 showed that the two glycoproteins were retained in the endoplasmic reticulum and had the expected glycosylation patterns [29].
• Electrophoretic mobility-shift assays showed that the purified E2 protein bound with high affinity to E2BS-3 and weakly to the other putative E2BSs located within the viral long control region [30].

References